PROPOSAL SUMMARY My career goal is to become a leading academic scientist with a research focus on the neurophysiology of balance disorders in aging and age-related disease. I will achieve this goal by leading a translational research program aimed at identifying the pathophysiological manifestations of aging and age-related disease that diminish the control of walking and standing, and their consequences on important clinical outcomes such as mobility. I will also work to translate these discoveries into future clinical interventions and practices that will improve mobility and quality of life within these populations. The control of gait and posture is dependent upon cognition and is linked to prefrontal brain function in healthy adults. The proposed K99 phase research has been designed to, for the first time, study the effects of aging, type 2 diabetes mellitus (DM) and Alzheimer?s disease (AD) on prefrontal brain activation during standing and walking. Both DM and AD exaggerate age-related declines in gait and posture, and it is expected that this is caused at least in part by shared cerebrovascular complications; namely, a reduced ability to sufficiently activate the prefrontal cortex during these activities due to decrease blood flow and increased vascular resistance. With this information in hand, the proposed R00 phase research will then attempt to increase prefrontal brain activation using transcranial direct current stimulation (tDCS) in order to improve walking and standing in these patients. Thus, the following Specific Aims will be completed: K99 Aim 1 will determine, cross-sectionally, the relationship between gait and postural control and markers of brain activation during these activities in younger and older adults, as well as older adults with DM or AD. Brain activation markers (i.e., blood flow, blood oxygenation) will be quantified using transcranial Doppler ultrasound and functional near-infrared spectroscopy. We hypothesize that H1) those who exhibit slower gait speed when walking and greater postural sway speed when standing will exhibit less brain activation during these tasks and H2) brain activation during gait and postural control will be greatest in healthy young, lower in healthy old, and lowest in the disease groups. R00 Aim 2 will determine, using a 10-day tDCS intervention, a) the effects of tDCS targeting the prefrontal cortex on gait and postural control and brain activation, and b) the immediate and longer-term (i.e., over a one- month follow-up) effects on these outcomes in patients with DM or AD. Those who exhibit gait and postural control difficulties at baseline will be randomized into real or sham (i.e., control) tDCS intervention groups. We hypothesize that H3) the real tDCS group will exhibit an increase in gait speed when walking and reduction of postural sway speed when standing, and an increase in brain activation during these tasks, both immediately and over the 30-day follow-up period. Together, these discoveries will provide insight into the cerebrovascular control of gait and postural control in aging and age-related disease; and new therapeutic targets (i.e., blood flow and blood oxygenation) for balance rehabilitation. Moreover, it will identify tDCS as an important tool in balance research that may translate into a new low-cost and safe intervention for these vulnerable populations.